Transplant Outcomes Using Generic and Brand Name Immunosuppressants: studying medications used by people who have received kidney and liver transplants

7.摘要/项目摘要 自2009年以来，美国每年有超过28，000人接受器官移植。 免疫抑制药物对减少移植受者的排斥反应和移植物丢失至关重要。这些 药物可能是昂贵的，并且对患者造成经济负担，导致不依从。代以 昂贵的品牌药物与治疗等效、较便宜的仿制药是一种 潜在的解决方案，以克服财政障碍，改善获得和坚持免疫抑制剂。 然而，关于仿制药和品牌名称的治疗等效性存在问题 免疫抑制剂此外，仿制药之间没有相互比较;因此， 关于用一个仿制药替代另一个仿制药的问题。这种不确定性对于 寻求为患者提供最佳护理的临床医生。 为了检验非专利免疫抑制剂的效用，我们将研究肾和肝移植的受者 在2008年到2013年间。该项目的三个具体目标中的第一个是描述通用和 移植后使用品牌免疫抑制剂。这些模式将被检查的患者的时间，因为 移植，也按日历日期，仔细梳理除了发生的变化，因为病人的需要演变， 这些变化与通用免疫抑制剂的可用性变化一致。我们将描述 移植计划水平的模式，在患者中汇总，以了解计划水平 与通用免疫抑制剂采用速度相关的因素。为了解决我们的第二个具体问题， 目的是，我们将比较经活检证实和治疗的排斥反应和移植失败的风险， 品牌名免疫抑制剂。我们将使用时间依赖的考克斯回归模型来模拟这些风险， 控制受体、器官供体和移植手术特征之间的变异性。我们 将仔细检查患者亚组（包括儿科患者）治疗效果的异质性 成年人、少数种族和民族、女性和男性，以及医疗复杂性或更大的患者- 不良后果的平均风险。假设我们发现， 相对于品牌药物，我们的第三个目标是量化成本 与每种药物有关。我们将通过以下方式向患者和付款人展示节省的费用 使用非专利免疫抑制剂代替品牌免疫抑制剂。最终，我们希望 这项研究将提供关于使用通用名和品牌名的重要新见解， 免疫抑制剂，从而改善对移植受者的护理。

7. Abstract/Project Summary Each year since 2009, more than 28,000 people have received organ transplants in the United States. Immunosuppressive medications are critical to reduce rejection and graft loss in transplant recipients. These medications can be expensive and pose a financial burden to patients, leading to non-adherence. Substituting costly brand name medications with therapeutically equivalent, less expensive generic medications is a potential solution to overcome the financial barrier and improve access and adherence to immunosuppressants. However, there are questions regarding the therapeutic equivalence of generic and brand name immunosuppressants. In addition, generic products have not been compared with each other; thus, there is a concern regarding the substitution of one generic for another generic. This uncertainty is problematic for clinicians who seek to provide the best care for their patients. To examine the utility of generic immunosuppressants, we will study recipients of kidney and liver transplants between 2008 and 2013. The first of three specific aims of the project is to describe patterns of generic and brand immunosuppressant use after transplant. These patterns will be examined for patients by time since transplant and also by calendar date, to carefully tease apart changes that occur as patient needs evolve from changes that coincide with changes in the availability of generic immunosuppressants. We will describe patterns at the level of the transplant program, aggregated across patients, to understand program-level factors associated with the speed of generic immunosuppressant adoption. To address our second specific aim, we will compare risks of biopsy-proven and treated rejection and graft failure for patients on generic and brand name immunosuppressants. We will use time-dependent Cox regressions to model these risks, controlling for variability between recipients, organ donors, and characteristics of the transplant surgery. We will carefully examine heterogeneity of treatment effects in patient subgroups, including pediatric patients and adults, racial and ethnic minorities, women and men, and patients with medical complexities or greater- than-average risk for adverse outcomes. Assuming we find no meaningful difference in the effectiveness of generic medications relative to brand name medications, our third aim will be to quantify the costs associated with each type of medication. We will demonstrate the savings to patients and to payers through the use of generic immunosuppressants in place of brand name immunosuppressants. Ultimately, we expect that this study will provide significant new insights regarding the use of generic and brand name immunosuppressants, leading to improved care for transplant recipients.